Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Oncomed’

In our ECCO Preview series last year (note: ESMO and ECCO have alternated the EU major cancer conference in the Fall for years), we highlighted several promising novel agents in development including the following:

  • StemCentRx’s anti-DLL3 inhibitor: rovalpituzumab tesirine (ROVA-T)
  • Ignyta’s Pan Trk, ROS1 and ALK inhibitor: entrectinib
  • Pfizer’s anti-NOTCH3 inhibitor: PF–06650808
  • Pfizer’s PTK7 ADC in TNBC: PF–06647020

What happened to them all? Were they good selections or not?

Well, AbbVie acquired StemCentRx in a $10.2B deal, Ignyta are busy advertising their new clinical trial enrollment for entrectinib as a non-chemotherapy and non-placebo controlled study on social media, suggesting that compound’s clinical development is still very much alive, while both the Pfizer compounds are also still active, as far as I know.

None have yet been consigned to dog drug heaven, which is quite something considering the failure rate in oncology drug pipelines!

Indeed, last year the Pfizer PTK7 ADC data was focused on triple negative breast cancer, where there is a solid rationale. This time around, the same research group explore the latest activity in advanced solid tumours, including ovarian cancer, as mentioned in the earlier Preview (See: 9 key abstracts in Ovarian Cancer).

sallys-barSo it’s time to sit down and chew the fat on one of my favourite topics at conferences – Development Therapeutics.

Here we consider which other compounds – other than the Pfizer ADC – that are worthy of highlighting and watching out for this year?

There are certainly some curious and quite different (i.e. novel) approaches to look at.

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Macarons in shop windowWe’re all familiar by now with the idea of checkpoints that can be inhibitory (release the brake) or stimulatory (put the foot on the gas) on the immune system.

There are multiple checkpoint modulators in development, it’s becoming a bit like buying a macaron – which flavour do you want?

As the late Holbrook Kohrt said on the Novel Targets Podcast last year:

There are two types of checkpoint inhibitors, one checkpoint inhibitor are these series of markers that each of them when you target them, they will slow down the function of that cell. Now that’s a good thing if that cell is a suppressor cell, such as a regulatory T cell. Anti-CTLA-4, ipilimumab, the first approved immunotherapeutic monoclonal antibody targets these regulatory T cells. Essentially is this concept as you said of taking off the brake .

Now if you want to press on the gas pedal, you want to find a target that is essentially that actually increases the function of a cell you want to make work better…….

…. these ideas of the different checkpoint inhibitors, essentially we should really call them, checkpoint modulation, because the checkpoints can either be gas pedals or they can be brakes.

And ultimately, it’s a question about how do you combine them in a rational way so that way you’re not either pushing the car too hard or taking the brake off at a time when the car is rolling in the wrong direction.

So essentially, you need to do checkpoint modulation in a setting where you still have the steering wheel on your car to ensure it’s directed against the right cells, otherwise you’re going to get significant toxicity.”

Which is a good introduction to Day 5 of our Road to AACR 2016 mini-series.

Over the course of 12 days in the run up to the 2016 annual meeting of the American Association for Cancer Research (AACR), we’re taking a look at some of the areas we expect to hear more about in New Orleans.

In today’s post, which continues our look at some of novel cancer immunotherapy targets, we’re look at the modulation of GITR (glucocorticoid-induced tumor necrosis factor receptor related gene) and companies that are targeting this.

GITR was named as the 12th most promising cancer immunotherapy target by the National Cancer Institute (NCI) back in 2006.  Interestingly, high GITR expression can be found on both T cells and NK cells.

There are now several agonist antibodies in development and entering the clinic that seek to activate GITR, and new data is expected at AACR 2016.

What GITR pathway data is worth looking out for at AACR 2016?

If you want to know more about why GITR matters, and where it fits into the cancer immunotherapy landscape then do read more. 

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